Injuries to the central nervous system result in permanent disability and represent a major unmet challenge in medicine today. In addition to the devastating impact on patient quality of life, these injuries impose a large economic burden on society. Although substantial research efforts are underway to promote the regeneration of injured nerve cell axons, the re-establishment of functional neural circuits remains a distant goal. In contrast, little attention has been paid to the possibility that axons may be surgically repaired at the cellular level in the acute setting to reconstitute function. The barrier to this approach is of course the fact that the precise manipulation of axons as small as one micron in diameter is beyond our current surgical technology. However, it is precisely at this small length scale that micro and nanotechnology excel. In recent work, we developed prototype micro and nanodevices that utilize short-range electrokinetic phenomenon to demonstrate early technical proof of principle for this approach. In this application for EUREKA funding, we propose to critically examine axon micro-repair from a biological perspective in order to determine the true potential of this novel methodology for nerve injury treatment. We will specifically investigate to what degree axonal function is reconstituted after the fusion repair or splicing together of two axon segments. In particular we will address whether the propagation of action potential activity and axonal transport can be demonstrated to occur in axon segments that have been reconnected with one another. Microdevice-assisted reconstruction of axons represents a paradigm shift compared to conventional approaches of stimulating axon re-growth and regeneration after injury. The results from this study may provide the biological underpinnings to a potentially new method of nerve repair and help meet an urgent clinical need. PUBLIC HEALTH RELEVANCE: The experimental studies proposed in this EUREKA application explore the biological underpinnings for a potentially new method of nerve repair. Since medicine today offers no specific therapy that can reconstitute function after injuries to neural pathways, this project has direct relevance to an area of clinical need. [unreadable] [unreadable] [unreadable]